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1.
Nature ; 602(7898): 585-589, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-35197615

RESUMO

Fast radio bursts (FRBs) are flashes of unknown physical origin1. The majority of FRBs have been seen only once, although some are known to generate multiple flashes2,3. Many models invoke magnetically powered neutron stars (magnetars) as the source of the emission4,5. Recently, the discovery6 of another repeater (FRB 20200120E) was announced, in the direction of the nearby galaxy M81, with four potential counterparts at other wavelengths6. Here we report observations that localized the FRB to a globular cluster associated with M81, where it is 2 parsecs away from the optical centre of the cluster. Globular clusters host old stellar populations, challenging FRB models that invoke young magnetars formed in a core-collapse supernova. We propose instead that FRB 20200120E originates from a highly magnetized neutron star formed either through the accretion-induced collapse of a white dwarf, or the merger of compact stars in a binary system7. Compact binaries are efficiently formed inside globular clusters, so a model invoking them could also be responsible for the observed bursts.

2.
Nature ; 577(7789): 190-194, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31907402

RESUMO

Fast radio bursts (FRBs) are brief, bright, extragalactic radio flashes1,2. Their physical origin remains unknown, but dozens of possible models have been postulated3. Some FRB sources exhibit repeat bursts4-7. Although over a hundred FRB sources have been discovered8, only four have been localized and associated with a host galaxy9-12, and just one of these four is known to emit repeating FRBs9. The properties of the host galaxies, and the local environments of FRBs, could provide important clues about their physical origins. The first known repeating FRB, however, was localized to a low-metallicity, irregular dwarf galaxy, and the apparently non-repeating sources were localized to higher-metallicity, massive elliptical or star-forming galaxies, suggesting that perhaps the repeating and apparently non-repeating sources could have distinct physical origins. Here we report the precise localization of a second repeating FRB source6, FRB 180916.J0158+65, to a star-forming region in a nearby (redshift 0.0337 ± 0.0002) massive spiral galaxy, whose properties and proximity distinguish it from all known hosts. The lack of both a comparably luminous persistent radio counterpart and a high Faraday rotation measure6 further distinguish the local environment of FRB 180916.J0158+65 from that of the single previously localized repeating FRB source, FRB 121102. This suggests that repeating FRBs may have a wide range of luminosities, and originate from diverse host galaxies and local environments.

3.
Nature ; 553(7687): 182-185, 2018 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-29323297

RESUMO

Fast radio bursts are millisecond-duration, extragalactic radio flashes of unknown physical origin. The only known repeating fast radio burst source-FRB 121102-has been localized to a star-forming region in a dwarf galaxy at redshift 0.193 and is spatially coincident with a compact, persistent radio source. The origin of the bursts, the nature of the persistent source and the properties of the local environment are still unclear. Here we report observations of FRB 121102 that show almost 100 per cent linearly polarized emission at a very high and variable Faraday rotation measure in the source frame (varying from +1.46 × 105 radians per square metre to +1.33 × 105 radians per square metre at epochs separated by seven months) and narrow (below 30 microseconds) temporal structure. The large and variable rotation measure demonstrates that FRB 121102 is in an extreme and dynamic magneto-ionic environment, and the short durations of the bursts suggest a neutron star origin. Such large rotation measures have hitherto been observed only in the vicinities of massive black holes (larger than about 10,000 solar masses). Indeed, the properties of the persistent radio source are compatible with those of a low-luminosity, accreting massive black hole. The bursts may therefore come from a neutron star in such an environment or could be explained by other models, such as a highly magnetized wind nebula or supernova remnant surrounding a young neutron star.

4.
Nature ; 541(7635): 58-61, 2017 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-28054614

RESUMO

Fast radio bursts are astronomical radio flashes of unknown physical nature with durations of milliseconds. Their dispersive arrival times suggest an extragalactic origin and imply radio luminosities that are orders of magnitude larger than those of all known short-duration radio transients. So far all fast radio bursts have been detected with large single-dish telescopes with arcminute localizations, and attempts to identify their counterparts (source or host galaxy) have relied on the contemporaneous variability of field sources or the presence of peculiar field stars or galaxies. These attempts have not resulted in an unambiguous association with a host or multi-wavelength counterpart. Here we report the subarcsecond localization of the fast radio burst FRB 121102, the only known repeating burst source, using high-time-resolution radio interferometric observations that directly image the bursts. Our precise localization reveals that FRB 121102 originates within 100 milliarcseconds of a faint 180-microJansky persistent radio source with a continuum spectrum that is consistent with non-thermal emission, and a faint (twenty-fifth magnitude) optical counterpart. The flux density of the persistent radio source varies by around ten per cent on day timescales, and very long baseline radio interferometry yields an angular size of less than 1.7 milliarcseconds. Our observations are inconsistent with the fast radio burst having a Galactic origin or its source being located within a prominent star-forming galaxy. Instead, the source appears to be co-located with a low-luminosity active galactic nucleus or a previously unknown type of extragalactic source. Localization and identification of a host or counterpart has been essential to understanding the origins and physics of other kinds of transient events, including gamma-ray bursts and tidal disruption events. However, if other fast radio bursts have similarly faint radio and optical counterparts, our findings imply that direct subarcsecond localizations may be the only way to provide reliable associations.

5.
Nature ; 531(7593): 202-5, 2016 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-26934226

RESUMO

Fast radio bursts are millisecond-duration astronomical radio pulses of unknown physical origin that appear to come from extragalactic distances. Previous follow-up observations have failed to find additional bursts at the same dispersion measure (that is, the integrated column density of free electrons between source and telescope) and sky position as the original detections. The apparent non-repeating nature of these bursts has led to the suggestion that they originate in cataclysmic events. Here we report observations of ten additional bursts from the direction of the fast radio burst FRB 121102. These bursts have dispersion measures and sky positions consistent with the original burst. This unambiguously identifies FRB 121102 as repeating and demonstrates that its source survives the energetic events that cause the bursts. Additionally, the bursts from FRB 121102 show a wide range of spectral shapes that appear to be predominantly intrinsic to the source and which vary on timescales of minutes or less. Although there may be multiple physical origins for the population of fast radio bursts, these repeat bursts with high dispersion measure and variable spectra specifically seen from the direction of FRB 121102 support an origin in a young, highly magnetized, extragalactic neutron star.

6.
Phys Rev Lett ; 127(18): 182501, 2021 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-34767384

RESUMO

The validity of the Brink-Axel hypothesis, which is especially important for numerous astrophysical calculations, is addressed for ^{116,120,124}Sn below the neutron separation energy by means of three independent experimental methods. The γ-ray strength functions (GSFs) extracted from primary γ-decay spectra following charged-particle reactions with the Oslo method and with the shape method demonstrate excellent agreement with those deduced from forward-angle inelastic proton scattering at relativistic beam energies. In addition, the GSFs are shown to be independent of excitation energies and spins of the initial and final states. The results provide a critical test of the generalized Brink-Axel hypothesis in heavy nuclei, demonstrating its applicability in the energy region of the pygmy dipole resonance.

7.
Nature ; 497(7451): 591-3, 2013 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-23719460

RESUMO

Magnetars are neutron stars with X-ray and soft γ-ray outbursts thought to be powered by intense internal magnetic fields. Like conventional neutron stars in the form of radio pulsars, magnetars exhibit 'glitches' during which angular momentum is believed to be transferred between the solid outer crust and the superfluid component of the inner crust. The several hundred observed glitches in radio pulsars and magnetars have involved a sudden spin-up (increase in the angular velocity) of the star, presumably because the interior superfluid was rotating faster than the crust. Here we report X-ray timing observations of the magnetar 1E 2259+586 (ref. 8), which exhibited a clear 'anti-glitch'--a sudden spin-down. We show that this event, like some previous magnetar spin-up glitches, was accompanied by multiple X-ray radiative changes and a significant spin-down rate change. Such behaviour is not predicted by models of neutron star spin-down and, if of internal origin, is suggestive of differential rotation in the magnetar, supporting the need for a rethinking of glitch theory for all neutron stars.

8.
Science ; 290(5495): 1347-51, 2000 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-11082060

RESUMO

TNAs [(L)-alpha-threofuranosyl oligonucleotides] containing vicinally connected (3'-->2') phosphodiester bridges undergo informational base pairing in antiparallel strand orientation and are capable of cross-pairing with RNA and DNA. Being derived from a sugar containing only four carbons, TNA is structurally the simplest of all potentially natural oligonucleotide-type nucleic acid alternatives studied thus far. This, along with the base-pairing properties of TNA, warrants close scrutiny of the system in the context of the problem of RNA's origin.


Assuntos
Pareamento de Bases , Ácidos Nucleicos/química , Oligonucleotídeos/química , RNA/química , Tetroses/química , Configuração de Carboidratos , DNA/química , Evolução Química , Hidrólise , Conformação de Ácido Nucleico , Ácidos Nucleicos Heteroduplexes , Ácidos Nucleicos/síntese química , Oligonucleotídeos/síntese química
10.
Sci Rep ; 8(1): 7948, 2018 05 21.
Artigo em Inglês | MEDLINE | ID: mdl-29784952

RESUMO

Many of the world's largest rivers in the extra tropics are covered with ice during the cold season, and in the Northern Hemisphere approximately 60% of the rivers experience significant seasonal effects of river ice. Here we present an observational data set of the ice cover regime for the lower part of the Danube River which spans over the period 1837-2016, and its the longest one on record over this area. The results in this study emphasize the strong impact of climate change on the occurrence of ice regime especially in the second part of the 20th century. The number of ice cover days has decreased considerably (~28days/century) mainly due to an increase in the winter mean temperature. In a long-term context, based on documentary evidences, we show that the ice cover occurrence rate was relatively small throughout the Medieval Warm Period (MWP), while the highest occurrence rates were found during the Maunder Minimum and Dalton Minimum periods. We conclude that the river ice regime can be used as a proxy for the winter temperature over the analyzed region and as an indicator of climate-change related impacts.

11.
Ophthalmologe ; 115(9): 785-792, 2018 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-29971474

RESUMO

BACKGROUND: The therapeutic principle of examinations of children under general anaesthesia using microscope-integrated optical coherence tomography (MI-OCT) is presented. The aim was to assess novel indications as well as limitations for MI-OCT to enhance ophthalmological examinations of neonates and children under general anesthesia. METHODS: The study was based on a review of the literature from google.scholar.com and PubMed and our own data from a prospective study (Department for Ophthalmology, University of Cologne) of 14 children with anterior and posterior segment anomalies undergoing examinations under anesthesia. Patients were examined using a commercially available MI-OCT device. The study analyzed the general feasibility of MI-OCT for ophthalmological examination of children under general anesthesia for the anterior and posterior eye segments and the benefits of indications and intraoperative findings. RESULTS: The MI-OCT significantly enriched the examinations of children under general anesthesia and delivered additional information not visible with the surgical microscope. Even in situations with a limited anterior chamber view MI-OCT enabled estimation of distances, such as corneal thickness. In addition to influencing therapeutic decisions, in 12/14 children MI-OCT also enabled examination of the thickness of the nerve fibre layer of the optic nerve disc and the retina. CONCLUSION: The data presented here underline the benefit of the intraoperative MI-OCT in ophthalmological examinations of children under general anesthesia. In particular MI-OCT enables examinations of children with corneal opacification, if an ophthalmological examination under general anesthesia becomes necessary.


Assuntos
Disco Óptico , Segmento Posterior do Olho , Tomografia de Coerência Óptica , Criança , Humanos , Recém-Nascido , Microscopia , Estudos Prospectivos
12.
J Clin Invest ; 98(3): 838-45, 1996 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-8698876

RESUMO

Left ventricular hypertrophy (LVH) produced by aortic valve plication leads to increased myocardial cyclic GMP. We tested whether this was a result of increased soluble guanylate cyclase activity or nitric oxide (NO) synthase and its functional consequences. We used the nitric oxide donor 3-morpholino-sydnonimine (SIN-1) or the NO synthase inhibitor NG-nitro-l-arginine methyl ester (L-NAME) in 12 control and 12 LVH anesthetized open-chest mongrel dogs. L-NAME (6 mg/kg) or SIN-1 (1 microgram/kg per min) was infused into the left anterior descending coronary artery and regional segment work and cyclic GMP levels were determined. In vitro myocardial guanylate cyclase sensitivity (0.43 +/- 0.04 to 0.28 +/- 0.04 mM [EC50]) and maximal activity (10.1 +/- 2.9 to 25.5 +/- 6.5 pmol/mg protein per min) were significantly increased in LVH as compared with control animals in response to nitroprusside stimulation, but cyclic GMP-phosphodiesterase activity was similar. In LVH dogs, basal cyclic GMP was significantly elevated in vivo when compared with controls. Treatment of dogs with SIN-1 resulted in a significant increase in cyclic GMP in control (1.09 +/- 0.12 to 1.48 +/- 0.19 pmol/gram) and a greater increase in the LVH group (1.78 +/- 0.16 to 3.58 +/- 0.71 pmol/g). L-NAME had no effect on myocardial cyclic GMP levels in control or LVH dogs. Segment work decreased in the control group after SIN-1 (1,573 +/- 290 to 855 +/- 211 grams x mm/min). LVH dogs showed no decrement in work as a result of treatment with SIN-1. L-NAME did not cause significant changes in myocardial cyclic GMP, O2 consumption, or work in either control or LVH dogs, but vascular effects were evident. SIN-1 increased cyclic GMP, and with greater effect on LVH; however, this resulted in a decrement in function only in the control group. The greater increased cyclic GMP in LVH dogs is not related to increased NO production, but is related to significantly higher sensitivity and maximal activity of soluble myocardial guanylate cyclase.


Assuntos
GMP Cíclico/biossíntese , Guanilato Ciclase/metabolismo , Hipertrofia Ventricular Esquerda/metabolismo , Animais , Arginina/análogos & derivados , Arginina/farmacologia , Cães , Feminino , Masculino , Molsidomina/análogos & derivados , Molsidomina/farmacologia , NG-Nitroarginina Metil Éster , Consumo de Oxigênio
13.
Animal ; 11(2): 254-260, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27406177

RESUMO

A truthful snapshot of horse welfare conditions is a prerequisite for predicting the impact of any actions intended to improve the quality of life of horses. This can be achieved when welfare information, gathered by different assessors in diverse geographical areas, is valid, comparable and collected in a harmonized way. This paper aims to present the first outcomes of the Animal Welfare Indicators (AWIN) approach: the results of on-farm assessment and a reliable and harmonized data collection system. A total of 355 sport and leisure horses, stabled in 40 facilities in Italy and in Germany, were evaluated by three trained assessors using the AWIN welfare assessment protocol for horses. The AWINHorse app was used to collect, store and send data to a common server. Identified welfare issues were obesity, unsatisfactory box dimensions, long periods of confinement and lack of social interaction. The digitalized data collection was feasible in an on-farm environment, and our results suggest that this approach could prove useful in identifying the most relevant welfare issues of horses in Europe or worldwide.


Assuntos
Criação de Animais Domésticos/normas , Bem-Estar do Animal , Cavalos/fisiologia , Animais , Coleta de Dados , Alemanha , Itália , Qualidade de Vida , Esportes
14.
Eye (Lond) ; 30(10): 1371-1377, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27391938

RESUMO

PurposeTo compare the short-term treatment outcome of the 577 nm subthreshold micropulse laser (SML) and half-dose photodynamic therapy (PDT) in patients with chronic central serous chorioretinopathy (cCSC) and persistent subretinal fluid (SRF).MethodsThis retrospective study included 100 eyes of 100 consecutive patients who were treated with the 577 nm SML (Supra Scan, Quantel Medical) (n=42) or half-dose PDT (n=58) for cCSC. The treatment was applied at the leakage sites in the fluorescein and indocyanine green angiography. The treatment success was evaluated 6 weeks after treatment using best-corrected visual acuity, central retinal thickness, and resolution of SRF in spectral domain optical coherence tomography.ResultsPatients showed treatment response more often in the SML group compared with the PDT group (treatment response after SML: 33 eyes (79%), PDT: 34 eyes (59%), P=0.036, χ2 test). The CRT decreased significantly after both treatments (mean CRT before SML: 445±153 µm, after SML: 297±95, P<0.001; mean CRT before PDT: 398±88 µm, after PDT: 322±93 µm, P<0.001, Wilcoxon's signed-rank test). The decrease in CRT was statistically significantly higher in the SML group (decrease in CRT after SML: -148±163 µm, after PDT: -76±104 µm, P=0.041, Mann-Whitney U-test).ConclusionsBoth the half-dose PDT and the 577 nm SML are potent treatments for cCSC with persistent SRF. More patients showed treatment response to the SML treatment and SML leads to a greater decrease in CRT.


Assuntos
Coriorretinopatia Serosa Central/terapia , Fotocoagulação a Laser , Fotoquimioterapia , Adulto , Idoso , Permeabilidade Capilar/efeitos dos fármacos , Coriorretinopatia Serosa Central/tratamento farmacológico , Coriorretinopatia Serosa Central/fisiopatologia , Coriorretinopatia Serosa Central/cirurgia , Doença Crônica , Feminino , Angiofluoresceinografia , Humanos , Masculino , Pessoa de Meia-Idade , Fármacos Fotossensibilizantes/administração & dosagem , Porfirinas/administração & dosagem , Estudos Retrospectivos , Líquido Sub-Retiniano , Tomografia de Coerência Óptica , Verteporfina , Acuidade Visual/fisiologia
15.
Eye (Lond) ; 30(8): 1072-6, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27197870

RESUMO

PurposeTo analyze choroidal neovasularization (CNV) activity and recurrence patterns in patients with neovascular age-related macular degeneration (nAMD) treated with ranibizumab, and the correlation with individual intraocular vascular endothelial growth factor (VEGF) suppression time (VST).MethodsPost-hoc analysis of data from a prospective, non-randomized clinical study. Patients with nAMD treated with ranibizumab on a pro re nata regimen. Disease activity was analyzed monthly by spectral-domain optical coherence tomography and correlated with VSTs.ResultsOverall, 73 eyes of 73 patients were included in the study with a mean follow-up of 717 days (range: 412-1239 days). Overall, the mean CNV-activity-free interval was 76.5 days (range: 0-829 days). The individual range of the length of dry intervals was high. A total of 42% of patients had a range of more than 90 days. Overall, 16% of patients showed persistent activity. And 12% stayed dry after the initial ranibizumab treatment. No significant correlation was found between the CNV-recurrence pattern and VST (P=0.12).ConclusionsCNV activity in nAMD is irregular, which is reflected in the range of the duration of dry intervals and late recurrences. The biomarker VST solely seems not to be sufficient to explain recurrence pattern of CNV in all AMD patients.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Neovascularização de Coroide/diagnóstico , Ranibizumab/uso terapêutico , Degeneração Macular Exsudativa/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Neovascularização de Coroide/tratamento farmacológico , Feminino , Seguimentos , Humanos , Injeções Intravítreas , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Tomografia de Coerência Óptica , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Acuidade Visual , Degeneração Macular Exsudativa/tratamento farmacológico
16.
Sci Rep ; 6: 32881, 2016 09 13.
Artigo em Inglês | MEDLINE | ID: mdl-27619955

RESUMO

As a key persistent component of the atmospheric dynamics, the North Atlantic blocking activity has been linked to extreme climatic phenomena in the European sector. It has also been linked to Atlantic multidecadal ocean variability, but its potential links to rapid oceanic changes have not been investigated. Using a global ocean-sea ice model forced with atmospheric reanalysis data, here it is shown that the 1962-1966 period of enhanced blocking activity over Greenland resulted in anomalous sea ice accumulation in the Arctic and ended with a sea ice flush from the Arctic into the North Atlantic Ocean through Fram Strait. This event induced a significant decrease of Labrador Sea water surface salinity and an abrupt weakening of the Atlantic Meridional Overturning Circulation (AMOC) during the 1970s. These results have implications for the prediction of rapid AMOC changes and indicate that an important part of the atmosphere-ocean dynamics at mid- and high latitudes requires a proper representation of the Fram Strait sea ice transport and of the synoptic scale variability such as atmospheric blocking, which is a challenge for current coupled climate models.

17.
Biochim Biophys Acta ; 1429(2): 391-400, 1999 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-9989224

RESUMO

The aim of this study was to investigate the binding interactions of the human progesterone receptor (hPR) with its natural ligand. Therefore, a homology-derived model of the hPR ligand binding domain has been constructed and used to predict residues potentially involved in interactions with progesterone. These residues and the free cysteines have been mutated (in total 13 residues with 15 mutations). All exchanges have been designed to preserve the three-dimensional structure of the protein. With respect to the binding characteristics towards progesterone, the muteins fall into three groups displaying no, reduced, or wildtype-like binding activity.


Assuntos
Progesterona/metabolismo , Receptores de Progesterona/metabolismo , Sequência de Aminoácidos , Animais , Eletroforese em Gel de Poliacrilamida , Humanos , Modelos Moleculares , Dados de Sequência Molecular , Mutagênese Sítio-Dirigida , Mutação Puntual , Receptores de Progesterona/química , Receptores de Progesterona/genética , Alinhamento de Sequência
18.
Arch Intern Med ; 149(5): 1202-3, 1989 May.
Artigo em Inglês | MEDLINE | ID: mdl-2655545

RESUMO

Actinomycosis is typically a chronic infection of the cervicofascial, thoracic, or abdominal region. Involvement of the heart occurs but is unusual. We present a case of chronic constrictive pericarditis caused by actinomycetes. The actinomycosis infection was present for 20 years, thereby representing the longest duration reported in the literature, to our knowledge.


Assuntos
Actinomicose/diagnóstico , Pericardite Constritiva/diagnóstico , Doença Crônica , Humanos , Masculino , Pessoa de Meia-Idade , Pericardite Constritiva/etiologia
19.
Cardiovasc Res ; 36(3): 453-9, 1997 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-9534866

RESUMO

OBJECTIVES: We tested the hypothesis that a reduction in myocardial cyclic GMP would increase myocardial O2 consumption and that renal hypertension (One Kidney-One Clip, 1K1C)-induced cardiac hypertrophy would change this relationship. METHODS: Either vehicle or LY83583 (10(-3) M, a guanylate cyclase inhibitor) was topically applied to the left ventricular surface of control of 1K1C anesthetized open-chest New Zealand white rabbits (N = 38). Coronary blood flow (radioactive microspheres) and O2 extraction (microspectrophotometry) were used to determine subepicardial (EPI) and subendocardial (ENDO) O2 consumption and myocardial cyclic GMP was determined by radioimmunoassay. RESULTS: The heart weight/body weight ratio was greater in the 1K1C rabbits (3.16 +/- 0.20) than controls (2.58 +/- 0.08 g/kg). Systolic blood pressure was higher in 1K1C rabbits (116 +/- 8 mm Hg) than controls (80 +/- 6), but topical LY83583 had no significant hemodynamic effects. LY83583 significantly and similarly decreased EPI cyclic GMP in both control (7.9 +/- 1.2 to 6.0 +/- 1.0 pmol/g) and 1K1C (7.7 +/- 1.2 to 5.3 +/- 0.9) hearts and control ENDO (8.7 +/- 1.7 to 7.2 +/- 1.2) but not 1K1C ENDO (6.7 +/- 0.5 to 5.7 +/- 1.1). Myocardial O2 consumption was significantly increased in control with LY83583 (EPI 6.6 +/- 1.1 to 15.6 +/- 1.4 and ENDO 7.2 +/- 0.9 to 14.2 +/- 0.7 ml O2/min/100 g), but not in 1K1C hearts (EPI 12.1 +/- 1.0 to 12.9 +/- 1.2 or ENDO 11.4 +/- 0.7 to 12.9 +/- 0.9). CONCLUSIONS: Thus myocardial O2 consumption was only increased by LY83583 in control hearts, but LY83583 decreased cyclic GMP similarly in both the control and 1K1C EPI. This indicated, at least in the EPI, a dissociation of the inverse relationship between the myocardial level of cyclic GMP and O2 consumption in the 1K1C rabbit heart.


Assuntos
Cardiomegalia/metabolismo , GMP Cíclico/metabolismo , Hipertensão Renal/complicações , Miocárdio/metabolismo , Consumo de Oxigênio/efeitos dos fármacos , Aminoquinolinas/farmacologia , Análise de Variância , Animais , Cardiomegalia/etiologia , Circulação Coronária/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Guanilato Ciclase/antagonistas & inibidores , Hipertensão Renal/metabolismo , Masculino , Pericárdio/metabolismo , Coelhos
20.
Cardiovasc Res ; 28(9): 1360-5, 1994 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-7954646

RESUMO

OBJECTIVE: The aim was to test the hypothesis that local myocardial work and O2 consumption would respond differentially to milrinone, a selective cyclic AMP-phosphodiesterase inhibitor, in left ventricular hypertrophy due to differences in myocardial cyclic AMP-phosphodiesterase activity. METHODS: The effect of milrinone on regional segment work and regional O2 consumption was measured in 12 open chest anaesthetised dogs with left ventricular hypertrophy induced by valvular aortic stenosis and in 10 age matched control dogs. Regional myocardial work was calculated as the integrated product of instantaneous force development (miniature transducer) and segment shortening (sonomicrometer). Regional O2 consumption was calculated from coronary blood flow (radiolabelled microspheres) and O2 saturations in small regional vessels (microspectrophotometry). Low Km phosphodiesterase activity was assayed by measuring the hydrolysis of radiolabelled cyclic AMP. RESULTS: Milrinone increased left ventricular dP/dtmax by approximately 60-70% in both control [2808(SEM 314) to 4584(660) mm Hg.s-1] and left ventricular hypertrophy [3279(258) to 5589(470) mm-Hg.s-1]. Regional work increased significantly in control [612(88) to 955(101) g.mm.min-1], while the increase was not significant in left ventricular hypertrophy [859(139) to 974(172) g.mm.min-1]. Regional O2 consumption increased significantly with milrinone in left ventricular hypertrophy [8.1(1.2) to 13.1(2.4) ml O2.min-1.100 g-1], but the increase was not significant in control [6.9(1.2) to 7.4(1.0) ml O2.min-1.100 g-1]. Myocardial stiffness during ejection was increased by milrinone to a significantly greater extent in animals with left ventricular hypertrophy. These effects were not related to differences in cyclic AMP-phosphodiesterase activity between control hearts and hearts with left ventricular hypertrophy [393(45) v 402(36) pmol.mg protein-1.1]. CONCLUSIONS: Differences between the hypertrophied and normal canine myocardium in response to milrinone are either due to altered levels of cyclic AMP production in left ventricular hypertrophy, to effects of milrinone that are unrelated to cyclic AMP-phosphodiesterase inhibition, or to other differences in hypertrophied hearts. The greater stiffness of the myocardium in left ventricular hypertrophy may require a greater energy expenditure to increase the amount of work it performs.


Assuntos
3',5'-AMP Cíclico Fosfodiesterases/antagonistas & inibidores , Hipertrofia Ventricular Esquerda/metabolismo , Contração Miocárdica/efeitos dos fármacos , Miocárdio/metabolismo , Consumo de Oxigênio/efeitos dos fármacos , Inibidores de Fosfodiesterase/farmacologia , Piridonas/farmacologia , Animais , Estenose da Valva Aórtica/metabolismo , Modelos Animais de Doenças , Cães , Milrinona , Miocárdio/enzimologia
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